Chongqing Reproduction and Genetics Institute, Chongqing Health Center for Women and Children, No.64 Jin Tang Street, Yu Zhong District, Chongqing, 400013, China.
Chongqing Key Laboratory of Human Embryo Engineering, Chongqing, China.
J Assist Reprod Genet. 2022 Jan;39(1):117-125. doi: 10.1007/s10815-021-02368-x. Epub 2021 Nov 29.
We aimed to evaluate the link between the GDF9 concentration in day 3 human embryo culture medium and embryo quality and viability.
Two independent, prospective, observational studies were conducted. In study 1, a total of 280 embryos from 70 patients who obtained at least 4 embryos with 6-10 blastomeres (2 transferable and 2 non-transferable embryos) at day 3 were enrolled. In study 2, a total of 119 embryos from 61 patients (29 fully implanted and 32 non-implanted patients) were enrolled. The corresponding GDF9 concentrations in spent culture medium of embryos were quantified by ELISA assay. The expression pattern of GDF9 in human embryos was investigated using Q-PCR and immunofluorescence.
GDF9 mRNA and protein were detected from human oocytes to eight-cell embryos and displayed a slow decreasing trend. In study 1, GDF9 concentration in culture medium is lower for transferable embryos compared with non-transferable embryos (331 pg/mL (quartiles: 442, 664 pg/mL) vs. 518 pg/mL (quartiles: 328, 1086 pg/mL), P < 0.001), and increased commensurate with the diminution of the embryo quality (P < 0.001). In study 2, significantly lower GDF9 concentration was detected for implanted embryos than non-implanted embryos (331 pg/mL (quartiles: 156, 665 pg/mL) vs. 518 pg/mL (quartiles: 328, 1086 pg/mL), P < 0.001). The same trend was found between the embryos that led to live birth and those that failed.
The GDF9 concentration in culture medium is linked to embryo quality and viability, and exhibited the potential to be a non-invasive biomarker for embryo selection.
评估人胚胎培养第 3 天培养液中 GDF9 浓度与胚胎质量和活力之间的关系。
进行了两项独立的前瞻性观察研究。在研究 1 中,共纳入了 70 名患者的 280 个胚胎,这些患者在第 3 天获得了至少 4 个具有 6-10 个卵裂球的胚胎(2 个可移植胚胎和 2 个不可移植胚胎)。在研究 2 中,共纳入了 61 名患者的 119 个胚胎(29 个完全着床患者和 32 个未着床患者)。通过 ELISA 测定法对胚胎培养液中 GDF9 的相应浓度进行定量。使用 Q-PCR 和免疫荧光法研究 GDF9 在人胚胎中的表达模式。
从人类卵母细胞到 8 细胞胚胎均检测到 GDF9 mRNA 和蛋白,且呈缓慢下降趋势。在研究 1 中,与不可移植胚胎相比,可移植胚胎的培养液中 GDF9 浓度较低(331pg/mL(四分位数:442、664pg/mL)vs.518pg/mL(四分位数:328、1086pg/mL),P<0.001),且与胚胎质量的降低呈正相关(P<0.001)。在研究 2 中,与不可移植胚胎相比,着床胚胎的 GDF9 浓度显著较低(331pg/mL(四分位数:156、665pg/mL)vs.518pg/mL(四分位数:328、1086pg/mL),P<0.001)。在导致活产的胚胎和未活产的胚胎之间也发现了相同的趋势。
培养液中 GDF9 浓度与胚胎质量和活力相关,具有成为胚胎选择的非侵入性生物标志物的潜力。